Buprenorphine duration of action:: Mu-opioid receptor availability and pharmacokinetic and behavioral indices
Buprenorphine duration of action:: Mu-opioid receptor availability and pharmacokinetic and behavioral indices
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DOI：
10.1016/j.biopsych.2006.04.043
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发表时间：
2007-01-01
影响因子：
10.6
通讯作者：
Zubieta, Jon-Kar
中科院分区：
文献类型：
--
作者：
Greenwald, Mark;Johanson, Chris-Ellyn;Zubieta, Jon-Kar
背景资料：丁丙诺啡（BUP）在隔日给药时可有效治疗阿片类药物依赖，这可能是由于μ阿片受体（μ OR）的长期占用。本研究在10名海洛因依赖志愿者中检查了BUP在mu CR下的作用持续时间以及与药代动力学和药效学结果的相关性。（用正电子发射断层扫描和[C-11]-卡芬太尼测量）、血浆BUP浓度、阿片类戒断症状和氢吗啡酮阻滞在其他地方报道的一项研究中，在省略16 mg/d剂量的BUP后4、28、52和76小时测量了（HYD;海洛因样激动剂）效应。相对于维持BUP安慰剂的海洛因依赖志愿者，BUP后4、28、52和76小时的脑-脑μ OR可用性分别为30%、54%、67%和82%。感兴趣的区域显示出类似的效果。BUP的血浆浓度是时间依赖性的，戒断症状、二氧化碳敏感性和HYD阻断程度也是时间依赖性的。mu OR的可用性也与BUP血浆浓度、戒断症状和HYD阻断相关。结合我们之前的发现，似乎mu OR可用性预测药代动力学和药效学指标的变化，并且需要约50%-60%的BUP占用率才能充分抑制戒断症状（在不存在其他阿片类药物的情况下）和HYD阻断。
Background: Buprenorphine (BUP) is effective in the treatment of opioid dependence when given on alternating days, probably as a result of long-lasting occupation of mu opioid receptors (mu ORs). This study examined the duration of action of BUP at mu CRs and correlations with pharmacokinetic and pharmacodynamic outcomes in 10 heroin-dependent volunteers.Methods: Availability of mu OR (measured with positron emission tomography and [C-11]-carfentanil), plasma BUP concentration, opioid withdrawal symptoms, and blockade of hydromorphone (HYD; heroin-like agonist) effects were measured at 4, 28, 52, and 76 hours after omitting the 16 mg/d dose of BUP in a study reported elsewhere.Results: Relative to heroin-dependent volunteers maintained on BUP placebo, wbole-brain mu OR availability was 30%, 54%, 67%, and 82% at 4, 28, 52, and 76 hours after BUP. Regions of interest showed similar effects. Plasma concentrations of BUP were time dependent, as were withdrawal symptoms, carbon dioxide sensitivity and extent of HYD blockade. Availability of mu OR was also correlated with BUP plasma concentration, withdrawal symptoms, and HYD blockade.Conclusions. Together with our previous findings, it appears that mu OR availability predicts changes in pharmacokinetic and pharmacodynamic measures and that about 50%-60% BUP occupancy is required for adequate withdrawal symptom suppression (in the absence of other opioids) and HYD blockade.